Is Medical Treatment Too Gender Neutral?

Sunday's "60 Minutes" segment suggested that healthcare practitioners, researchers, and drug makers have been, with the exception of reproductive science, approaching male and female bodies as identical organisms. That report might be a little outdated, though, as pharmaco-metabolic differences between men and women may be under-researched, but they are not unrecognized.

The question remains: Have practitioners been treating male and female patients the same when they shouldn't? Or, have they come up with their own methods for addressing physiological differences between the genders?

We asked 10 clinicians, and here's what they had to say:

"Since the thalidomide scare in the 1960's, researchers have been reluctant to include pregnant women in medical studies, for fear that they might be pregnant and not yet know it," said Keith A. Eddleman, MD, director of obstetrics at Mount Sinai Hospital in New York City.

"But in the past several decades, the FDA has begun encouraging the inclusion of females in research like this, so we are going to be seeing more and more studies of this nature making headlines."

"This is a very active area of research, and gave rise to the entire field of pharmacogenetics, which explores genetic differences in metabolic pathways that can affect how a patient responds to medications," Alvarez said.

Eddleman agrees, "Very soon, however, gender will be only one thing that is important when a doctor prescribes a medication. With the monumental information coming from the Human Genome Project, doctors will soon be able to easily tell how an individual (female or male) will respond to a given medication based on their genetic makeup. This will help doctors tailor the right medication for the right patient at the right dose."

"This recent '60 Minutes' review of gender differences in prescribing practices highlights known medical information on these differences in heart attacks, aspirin, and Ambien [zolpidem]," said Stephen Russell, MD, associate professor of internal medicine at the University of Alabama at Birmingham.

Diana Bitner, MD, director of Women's Health Network at Spectrum Health in Grand Rapids, Mich., said she agrees with the "60 Minutes" segment to an extent. "There is much we do not know. As we prescribe medication and diagnose conditions, we have to be aware that women have signs, symptoms, and respond to drugs differently than men."

"I have diagnosed women with heart disease who thought they were having hot flashes, but instead were having sweats associated with a heart attack, clearly not a symptom a man would have," Bitner said.

Randy Wexler, MD, MPH, vice chair of the Clinical Services Department of Family Medicine Ohio State University Wexner Medical Center in Columbus, doesn't see gender differences as a new issue in practice either. "I think it has been understood for quite some time that men and women may have differing reactions to medications, at least anecdotally based on the types of complaints we get when a medication causes a side effect."

Gender and Drug Testing

"I do think we need a lot more data about gender difference in medications (and medications in pregnancy and in children too). For far too long, studies have been primarily on men," said Aaron Michelfelder, MD, vice-chair of family medicine at Loyola University Chicago.

Wexler explains, "Many medications are impacted by fat solubility or insolubility and, in addition to likely differences in metabolism, men and women have a difference in their body fat distribution which could impact how a medication works (or does not). The difficulty in knowing how this may vary is that, quite frankly, it is not something that is a required evaluation for FDA approval."

"In addition, we do not learn many things about medications until after they hit the market, and unless post-marketing analyses are done/required, we may never know what variances exist between men and women for a specific drug or drug class because one physician caring for patients will not per se recognize a trend, as you need larger numbers to know if it is a true effect or or not." Wexler said.

"In the past, most of the large trials were done on white male patients. We know that gender, race, and age can be a factor when considering medication dosages, medication response, and also disease processes. The problem is that we do not know all of the differences yet," said Josephine Dlugopolski-Gach, MD, assistant professor of internal medicine and pediatrics at Loyola University Chicago, said.

What's Going On in Practice?

Denniz Zolnoun, MD, MPH, a gynecologic surgeon at the UNC Health Care in Chapel Hill, noted that "in fact, there are unknown and undiscovered interactions between oral low-dose estradiol and number of heart medications. Because of this, I have been monitoring blood levels of estradiol on patients because it can build as high as 250 pg/cc."

Charles Ascher-Walsh, MD, director of gynecology, urogynecology, and minimally invasive surgery at the Icahn School of Medicine at Mount Sinai, says he is used to making adjustments for female patients, "Many of the medications I use are either exclusively or primarily used by women. There is not a large concern for the possible difference in gender response to these medications. If it's a new medication, I generally start with the lowest recommended dose and titrate up as needed and tolerated."

Dlugopolski-Gach agrees with Ascher-Walsh's "start low" method. "As a general rule it is important to research the known clinical data and always start with the lowest medication dose, see how the patient responds, and then increase if needed. I have had patients with nearly identical cholesterol levels respond quite differently to the same medication and dose: one will have a dramatic drop in the cholesterol and the other will hardly change."

Matthew Siedhoff, MD, a gynecologic surgeon at the UNC Health Care, said that "As we learn more about how women handle medications differently than men, I'm sure dosing recommendations will change our future practice."

A Pharmacist's Take

"There are large gaps in our knowledge about sex differences with regards to medication benefits and risks. It could be because pharmacokinetics, pharmacodynamics, and dosing needs are different in women," said Laura Borgelt, PharmD, Associate Professor at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences.

"Examples of pharmacokinetic differences include differences in weight, volume of distribution, metabolism and clearance; all of which affect how a medication is processed in the body."

"Metabolism in the liver, specifically through the cytochrome P450 system, is known to be different in women than men and therefore could affect a drug's concentration in the body. Renal clearance of medications can be slower as women tend to have lower glomerular filtration rates."

"Receptors, including hormone receptors, are different in women compared with men and could impact response to a medication. Given the large array of differences that exist, it is important to consider sex when evaluating potential benefits and risk of any medication and to acknowledge that much more research is needed to determine how sex influences the benefits, risks, and dosing of medications," Borgelt added.

Prime Time is a blog by staff writer Sarah Wickline Wallan for readers with an interest in primary care.

UPDATE: This article, originally published Feb. 10, 2014 at 7:30 p.m., was updated with new material (Feb. 11, 2014, at 1:35 p.m.).

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